Twin, family and adoption data document genetic contributions to the development of alcoholism, but the specific pathways for these heritable effects remain unknown. Genetic influences on alcohol use and abuse appear to be modulated by age and gender and, perhaps by an individual's drinking history, and the nature of heritable influences on alcohol use may be quite distinguishable from the genetic pathways that predispose to alcohol abuse. Developmental genetic analyses that exploit twin-family designs can elucidate heritable mechanisms in the use and abuse of alcohol. Using the resources of the Indiana University Twin Panel, we propose two complementary studies: One will assess genetic influences on acute reactions to ethanol in young adult twins; the other will evaluate genetic, familial and gender sources of variation in alcohol use and abuse in extensive and innovative twin-family studies. Over a three-year period, 300 like-sex co-twins, ages 21-26, equally split by gender and zygosity but differing in familial risk for alcoholism and individual drinking history, will be studied in a laboratory assessment of psychophysiological, behavioral and subjective response to an ethonal load; these data will evaluate heritable variance in susceptibility to alcohol as a pathway for genetic influences in the development of alcoholism. Concurrently, questionnaire studies of self-reported use of alcohol and of personality dimensions predictive of alcohol abuse will be made in large samples of twins, their sibs and parents, in the extended kinships of monozygotic twin parents, and in balanced pedigrees formed by a singleton college student, a sibling and both parents. Retest reliability of dependent measures in the laboratory protocol and of self-reported use of alcohol will be established from repeat testing of a subset of subjects in both studies. Jointly, these three data-sets will yield significant information on the nature and magnitude of familial influences on frequency and quantity of alcohol use in 2500-3000 adolescent and adult members of 450-600 families. Parameter estimation of these data will permit robust and novel analyses of maternal effects, assortative mating, and gene by age by gender interactions in the familial aggregation of alcohol use and abuse.